Method and apparatus for analyzing breath sample

ABSTRACT

Method and apparatus for analyzing a breath sample provide user-friendly operation and analysis. The method and apparatus provide automatic operation and coordination of operation of an absorbent sample tube, including desorbing means, a chromatographic precolumn, a chromatographic main column, a detector, a data processor, a sample receiving tube for receiving exhaled breath sample, a sample loop for aspirating a prescribed quantity of breath sample from the sample receiving tube, a sample valve, a standard gas reservoir, and a standard gas valve. All of the foregoing are operated automatically in such that start cycles, detector cycles, fault detection cycles, standardizing, analysis, shutdown and end cycles are performed in a way which allows straightforward and simple measurement of breath sample by a user.

RELATED APPLICATION

This application is a divisional of application Ser. No. 08/910,113,Aug. 13, 1997, allowed now U.S. Pat. No. 6,148,657 granted Nov. 21,2000.

FIELD OF THE INVENTION

The present invention relates to a method and an apparatus for analyzingconstituents contained in a breath sample by means of gas chromatograph.

DESCRIPTION OF THE RELATED ART

There is conventionally available an apparatus for analyzing a breathsample based on detection of alcohol. On the other hand, analysis ofconstituents of a sample by the use of a gas chromatograph is popularlyapplied. The conventional chromatograph is used by researchers orengineers well versed in handling of the equipment. There is availableno apparatus for automatically starting a gas chromatograph, analyzingand testing a sample, and then completing. For many of the users,therefore, the conventional chromatographic analysis apparatus is hardto use.

There is known no apparatus serving for clinical tests in the medicalarea by analyzing breath constituents. A breath analyzing apparatus forsuch medical tests should preferably be easily and automatically used bya test operator.

SUMMARY OF THE INVENTION

The present invention has an object to provide breath analyzingapparatus and method for analyzing a breath sample by means of a gaschromatographic column.

Another object of the invention is to provide breath analyzing apparatusand method which permit automatic and easy breath analysis of alow-concentration constituent such as pentane.

Further, another object of the invention is to provide breath analyzingapparatus and method which permit analysis of low-concentrationconstituents and high-concentration constituents by the use of a singlemain column and a detector.

Further, another object of the invention is to provide breath analyzingmethod and apparatus which permit perfect automation of start processinguntil the analyzing apparatus is ready to analyze.

Further, another object of the invention is to provide breath analyzingmethod and apparatus which permit perfect automation of shutdownprocessing upon completion of analysis and until supply of a carrier gasis discontinued.

Further, another object of the invention is to provide breath analyzingmethod and apparatus which permit automatic testing of deterioration ofthe column.

Furthermore, the present invention has an object to provide a breathanalyzing method and a compact apparatus for the application thereof,which permit automation of various steps, completion of analysis in ashorter period of time of analysis and is easy to use in the area ofclinical testing having needs different from those of laboratories.

Another object of the invention is to provide breath analyzing apparatusand method for carrying out measurement of a room interior environment,detection of a narcotic drug in vivo, and investigation of a cause offire.

To achieve these objects of the invention, the apparatus of theinvention comprises desorbing means for desorbing a breath sampleabsorbed into an absorbent sample tube, a chromatographic precolumn forpassing the breath sample desorbed from the absorbent sample tube in aretention time prescribed for each constituent, a chromatographic maincolumn for passing the breath sample having passed through theprecolumn, in a retention time prescribed for each constituent, adetector for detecting constituents having passed through the maincolumn, and a data processor for generating a chromatograph for theconstituents detected by the detector. As a result of presence of theprecolumn, when there are two constituents having different retentiontimes, there remains, after passage of one constituent, for examplepentane, through the main column, the other constituent such as hexanein the precolumn, thus permitting earlier completion of analysis bypurging the main column and the precolumn. Presence of the desorbingmeans permits satisfactory detection of low-concentration constituentscontained in the breath such as pentane, dimethyl sulfide and isoprene.

Further, the apparatus of the invention comprises a sample receivingtube for receiving the exhaled breath sample, a sample loop foraspirating a prescribed quantity of breath sample from the samplereceiving tube, and a sample valve which connects the sample loop andthe main column when a breath sample is aspirated into the sample loop.This makes it possible to sample a high-concentration constituent in thebreath such as acetone directly from the sample receiving tube andanalyze the sampled constituent by means of the main column.

The apparatus of the invention further comprises a standard gas bottlefor supplying a standard gas, and a standard gas valve which connectsthe standard gas bottle and the sample loop when testing sensitivity ofsaid-column. This permits automatic testing of the column.

In a preferred embodiment, the apparatus of the invention comprises aninterface having various buttons and a controller controlling start,analysis, testing and shutdown of the apparatus in response to aninstruction to the interface.

In another preferred embodiment, there is disclosed a method necessaryfor separating isoprene and pentane by the use of the foregoingapparatus.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a configurational view of an embodiment of the presentinvention;

FIG. 2 is the same view as FIG. 1 in which the sample valve is changed;

FIG. 3 illustrates the relationship between the controller and theindividual heaters;

FIGS. 4(A) and 4(B) are schematic sectional views of the sampling valve;

FIG. 5 is a configurational view of absorbing means;

FIG. 6 is a block diagram illustrating the configuration of anotherembodiment of the invention;

FIG. 7 is a block diagram illustrating the configuration of thecontroller;

FIG. 8 is a block diagram illustrating the configuration of temperaturecontrol means;

FIG. 9 is a block diagram illustrating the configuration of channelswitching means;

FIG. 10 is a flowchart illustrating a typical start processing using thetime;

FIG. 11 is a flowchart illustrating a typical and processing using thetime;

FIG. 12 is a time chart of the processing shown in FIGS. 10 and 11;

FIG. 13 is a flowchart illustrating another example of start processingusing the time;

FIG. 14 is a flowchart illustrating another example of end processingusing the time;

FIG. 15 is a time chart of the processing shown in FIGS. 13 and 14;

FIG. 16 is a flowchart illustrating an example of start processing usingthe time;

FIG. 17 is a flowchart illustrating an example of end processing usingthe time;

FIG. 18 is a time chart of the processing shown in FIGS. 16 and 17;

FIG. 19 is a flowchart illustrating an example of test processing;

FIG. 20 is a graph illustrating typical conditions for conditioning;

FIG. 21 is a time chart;

FIG. 22 is a flowchart illustrating a typical analysis processing;

FIG. 23 is a flowchart illustrating an example of desorbing processing;

FIG. 24 is a chromatograph illustrating retention times for pentane andhexane;

FIGS. 25(A)-25(D) are descriptive views illustrating examples ofbacklash;

FIG. 26 is a configurational view of other embodiment of an apparatusnot having a sample receiving tube;

FIG. 27 is a view similar to FIG. 26, in which the sample valve ischanged;

FIGS. 28(A) and 28(B) are schematic sectional views of the samplingvalve;

FIGS. 29(A) and 29(B) are chromatographs for illustrating resolutionsR12, R23 and R34;

FIG. 30 is a graph illustrating retention times for the individualconstituents relative to temperature of the capillary column in acapillary column having a length of 10 [m] with a carrier gas flow ratekept constant at 5 [ml/min.];

FIG. 31 is a graph illustrating retention times for the individualconstituents relative to carrier gas flow rate in a capillary columnhaving a length of 10 [m] with a capillary column temperature keptconstant at 110° C.;

FIG. 32 is a graph illustrating retention times for the individualconstituents relative to carrier gas flow rate in a capillary columnhaving a length of 10 [m] with a capillary column temperature keptconstant at 130° C.;

FIG. 33 is a graph illustrating resolutions for the individualconstituents relative to capillary column temperature in a capillarycolumn having a length of 10 [m] with a carrier gas flow rate keptconstant at 5 [ml/min.];

FIG. 34 is a graph illustrating resolutions for the individualconstituents relative to carrier gas flow rate in a capillary columnhaving a length of 10 [m] with a capillary column temperature keptconstant at 110° C.;

FIG. 35 is a graph illustrating resolutions for the individualconstituents relative to carrier gas flow rate in a capillary columnhaving a length of 10 [m] with a capillary column temperature keptconstant at 130° C.;

FIG. 36 is a graph illustrating relative retention times for theindividual constituents relative to capillary column temperature in acapillary column having a length of 10 [m] with a carrier gas flow ratekept constant at 5 [ml/min.];

FIG. 37 is a graph illustrating retention times for the individualconstituents relative to capillary column temperature in a capillarycolumn haviang a length of 25 [m] with a carrier gas flow rate keptconstant at 5 [ml/min.];

FIG. 38 is a graph illustrating retention times for the individualconstituents relative to carrier gas flow rate in a capillary columnhaving a length of 25 [m] with a capillary column temperature keptconstant at 100° C.;

FIG. 39 is a graph illustrating retention times for the individualconstituents relative to carrier gas flow rate in a capillary columnhaving a length of 25 [m] with a capillary column temperature keptconstant at 110° C.;

FIG. 40 is a graph illustrating resolutions for the individualconstituents relative to capillary column temperature in a capillarycolumn havinag a length of 25 [m] with a carrier gas flow rates keptconstant at 5 [ml/min.] ;

FIG. 41 is a graph illustrating resolutions for the individualconstituents relative to carrier gas flow rate in a capillary columnhaving a length of 25 [m] with a capillary column temperature keptconstant at 100 ° C.;

FIG. 42 is a graph illustrating resolutions for the individualconstituents relative to carrier gas flow rate in a capillary columnhaving a length of 25 [m] with a capillary column temperature keptconstant at 110° C.; and

FIG. 43 is a graph illustrating relative retention times for theindividual constituents relative to capillary column temperature in acapillary column having a length of 25 [m] with a carrier gas flow ratekept constant at 5 [ml/min.] .

FIG. 44 is a chromatograph in a capillary column having a length of 10[m] with a carrier gas flow rate kept constant at 5 [ml/min.] and acapillary column temperature kept constant at 90° C.;

FIG. 45 is a chromatograph in a capillary column having a length of 10[m] with a carrier gas flow rate kept constant at 5 [ml/min.] and acapillary column temperature kept constant at 110° C.;

FIG. 46 is a chromatograph in a capillary column having a length of 10[m] with a carrier gas flow rate kept constant at 5 [ml/min.] and acapillary column temperature kept constant at 130° C.;

FIG. 47 is a chromatograph in a capillary column having a length of 10[m] with a carrier gas flow rate kept constant at 5 [ml/min.] and acapillary column temperature kept constant at 150° C.;

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Overview

Referring to FIG. 1, the breath analyzing apparatus 12 of the inventioncomprises a main column 14 and a precolumn 16 for passing a breathsample A therethrough and separating constituents contained in thebreath sample A, and a detector 56 for detecting the constituentsseparated by the precolumn 16 and the main column 14. The detector 56may be any of ones detecting mass, thermal conductivity, and ioncurrent.

The apparatus 12 further comprises an absorbent sample tube 22 absorbingthe breath sample A in the interior thereof, and desorbing means 20desorbing the breath sample A absorbed in the absorbent sample tube 22.Low-concentration constituents contained in the breath sample areintroduced from the desorbing means into the column. The apparatus 12 isfurther provided with a sample receiving tube 32 receiving a breath Bbreathed out by a subject, a sample loop 18 aspirating the breath B in acertain quantity, and a pump 66 aspirating the breath B in the samplereceiving tube 32 though the sample loop 18. High-concentrationconstituents of the breath sample are introduced from the samplereceiving tube and the sample loop into the column 14.

The apparatus 12 further comprises a standard gas bottle 62. Thestandard gas bottle 62 is filled with a standard gas S comprising knownconstituents. The standard gas is a mixture of, for example, helium withisoprene and pentane. Isoprene and pentane should have the sameconcentrations as in desorbing the breath sample at the desorbing means20 f. Standard gas storing means 69 is a storage vessel for storing thestandard gas in a certain quantity (for example, 500 ml) to ensuresmooth supply of the standard gas S. Bringing the standard gas intocontact with the breath analyzing apparatus is useful for testingresolution of the column or for confirming the retention time.

The breath analyzing apparatus of the invention further compriseschannel switching means 40. The channel switching means 40 has a samplevalve 42, a standard gas valve 43, solenoid valves 46, 48 and 50, and acontroller for switching over the individual solenoid valves 46, 48 and50 and the individual valves 42 and 43. The controller 44 may be onecomprising manual switches, one comprising relays and timers, or onecomprising a microcomputer and programs thereof. A carrier gas bottle 60filled with a carrier gas C is connected through a reducing valve 68 tothe channel switching means 40. Air, hydrogen, nitrogen, helium or argonis usually used as a carrier gas C.

The sample valve 42 selects any one of the desorbing means 20 and thesample receiving tube 32. The sample valve has a plurality of portsserving as outlets, ten ports in the example shown in FIG. 1. The samplevalve has two operating positions: FIG. 1 shows the first operatingposition and FIG. 2 shows the second operating position. In FIG. 1, theport 1 is connected to the port 2, the port 3 is connected to the port4, and similarly all the ports up to the port 10 are sequentiallyconnected. In FIG. 2, on the other hand, the port 2 is connected to theport 3, the port 4 is connected to the port 5, and all the ports aresequentially connected by shifting by one from the first operatingposition.

The standard gas valve 43 comprises an inlet connected to the samplereceiving tube 32, an inlet connected to the standard gas bottle 62, anoutlet connected to the sample valve 42, and a line connecting any oneof the inlets to the outlet by switching.

The desorbing means 20 comprises an absorbent sample tube support 24supporting the absorbent sample tube 22, a secondary concentrating tube26 absorbing the breath sample A in the interior thereof, and asecondary concentrating tube support 28 supporting the secondaryconcentrating tube 26. The absorbent sample tube support 24 has abuilt-in absorbent sample tube heater, described further in connectionwith FIG. 5 for desorbing the breath sample A absorbed in the absorbentsample tube 22. The secondary concentrating tube support 28 has asecondary concentrating tube cooler 26H for absorbing the breath sampleA desorbed from the absorbent sample tube 22 into the secondaryconcentrating tube 26, and a secondary concentrating tube heater,described further in connection with FIG. 5, for desorbing the breathsample A absorbed in the secondary concentrating tube 26 by heating thesecondary concentrating tube 26. The heater is for example an electricheater, and the cooler performs cooling by the use of liquid nitrogenfor example.

A capillary tube having an inside diameter within a range of from 0.5 to1.0 mm is used as the secondary concentrating tube 26. The materialshould preferably be the same as, or equivalent in properties with, thatof the main column 14. The secondary concentrating tube 26 should becoated with a liquid absorbent to improve efficiency of secondaryconcentration.

The sample receiving tube 32 has a breath discharging port 34 and abreath blowing port 36. The subject attaches a disposable mouth piece 38to the breath blowing port 36, presses the mouth piece 38 against his orher mouth, and blows a breath B into the sample receiving tube 32. Thesample receiving tube support 39 supports the sample receiving tube 32,and has a receiving tube heater for heating the breath B or the like.

Referring again to FIG. 1, the breath analyzing apparatus 12 has abreath sucking line for sucking a breath breathed out by the subjectthrough the ports 5 and 6 into the sample loop, to analyze the breathbreathed out by the subject.

Referring to FIG. 2, the apparatus 12 has a first carrier gas linecarrying the breath sucked into the sample loop to the sample valve 42,the main column 14, and the detector 56 by means of a pump. When thesolenoid valve 46 is open, the first carrier gas line sends the carriergas through the ports 7 and 6 to the sample loop, and sends the blownout breath through the ports 3 and 2 to the main column.

As shown in FIG. 1, the apparatus 12 has a second carrier gas line forcarrying the breath sample desorbed from the absorbent sample tube 22 tothe sample valve 42, the precolumn 16, the main column 14 and thedetector 56, to analyze the breath sample concentrated in the absorbentsample tube 22. When the solenoid valve 50 is open, the carrier gas linesends the carrier gas from the desorbing means 20 to the ports 10 and 9,the precolumn 16, the ports 1 and 2 and the main column 14.

The first carrier gas line serves also as a third carrier gas line forcarrying the standard gas sucked into the sample loop 18 to the samplevalve 42, the main column 14 and the detector 56.

Referring to FIG. 2, the apparatus 12 is further provided with a fourthcarrier gas line C2 which carries the constituents having passed throughthe precolumn 16 of the breath sample desorbed from the absorbent sampletube 22 to the sample valve 42, and the main column 14, and a fifthcarrier gas line C3 which purges the constituents not having passedthrough the precolumn 16 of the breath desorbed from the absorbentsample tube 22 from the sample valve 42. When performing backflash, thesecond carrier gas line C1 shown in FIG. 1 is switched over to thefourth and the fifth carrier gas lines C2 and C3 shown in FIG. 2.

Referring to FIG. 3, the apparatus 12 is further provided with a columnheater 14H heating the column 14, a detector heater 56H heating thedetector 56, a sample receiving tube heater 32H heating the samplereceiving tube 32, and a thermostatic oven 42H heating the sample loop18 and the sample valve 42. The controller 44 controls temperature ofthe individual heaters. A display 34 for displaying the test result orthe completion of start processing using the standard gas is connectedto the foregoing controller 44.

Referring to FIG. 4, the sampling valve 42 is a rotary valve having tenports 1 to 10. FIG. 4 is a schematic sectional view illustrating anexample of sampling valve 42. In FIG. 4, the sampling valve 42 iscomposed of a fixed body 42A having ports 1 to 10, a rotating body 42Bhaving communicating vessels a to e, and an actuator (not shown) such asa solenoid for rotating the rotating body 42B. FIG. 4(A) illustrates afirst operating position shown in FIG. 1, and FIG. 4(B) illustrates asecond operating position shown in FIG. 2.

Referring again to FIG. 1, a piping 1 a connected to an end of theprecolumn 16 is connected to the port 1. A piping 2 a connected to anend of the main column 14 is connected to the port 2. A piping 3 aconnected to an end of the sample loop 18 is connected to the port 3. Apiping 4 a connected to the pump 66 is connected to the port 4. A piping5 a connected to the sample receiving tube 32 is connected to the port5. A piping 6 a connected to the other end of the sample loop 18 isconnected to the port 6. A piping 7 a for introducing the carrier gas C2through the solenoid valve 46 is connected to the port 7. A piping 8 a(vent) for discharging the carrier gas C3 having passed through thedesorbing means 20 and the precolumn 16 is connected to the port 8. Apiping 9 a connected to the other end of the precolumn 16 is connectedto the port 9. A piping 10 a introducing the carrier gas C1 and C3having passed through the desorbing means via a filter 20 is connectedto the port 10.

Referring to FIG. 5, the breath concentrating/absorbing unit 80 forabsorbing the breath sample A into the absorbent sample tube 22comprises a Teddler bag 72 filled with breath A, the absorbent sampletube 22 connected to the Teddler bag 72, and a pump 84 for sucking thebreath A in the Teddler bag 72 into the absorbent sample tube 22.

Further, the breath concentrating/absorbing unit 80 is provided with amass flowmeter 86 for measuring a mass flow rate f of the breath Apassing through the absorbent sample tube 22, a manometer 81 formeasuring pressure p of the breath A in the Teddler bag 72, anabsorption control means 90 for stopping the pump 84 when pressure p ofthe breath A measured by the manometer 81 is under a prescribed valuepF, a thermostat 92 for keeping a constant temperature T of theabsorbent sample tube 22, and a water absorbing filter 94 provided inthe channel of the breath A between the absorbent sample tube 22 and thepump 84.

The Teddler bag 72, a tee 881 of the manometer 81, the absorbent sampletube 22, the water absorbing filter 94, the pump 84 and the massflowmeter 86 are individually connected by flexible tubes 95 a to 95 e.

The absorbent tube 22 has an absorbent 23 for absorbing the breathsample A. The Teddler bag 72 has a breath inlet port 74 and a breathdischarging port 78. A stop valve capable of being manually opened andclosed is provided for each of the breath discharging port 78 and thebreath inlet port 76. The subject previously attaches the disposablemouth piece 74 to the breath inlet port 76, presses his or her mouthagainst the mouth piece 74, and blows breath A into the Teddler bag 82.The mass flowmeter 86 is a common flowmeter for gas such as a massflowmeter. The manometer 81 utilizes the piezo-electric effect in whichvoltage is generated by applying a pressure onto a piezo-electricelement.

According to the result of an experiment, pressure p during sucking is,for example, −0.05 kgf/cm², and pressure p upon completion of suckingis, for example, within a range of from −0.3 to −0.4 kgf/cm². Todetermine the completion of sucking, pressure is measured with themanometer 81. The thermostat 92 is composed of a heating/cooling unit 96and a temperature control unit 97. The heating/cooling unit 96 can bedivided into an upper portion 98 and a lower portion 99, and the upperportion 98 and the lower portion 99 hold the absorbent sample tube 22 inbetween. The upper portion 98 has a heat insulating member 98A and aheat conducting member 98B. The lower portion 99 has a heat insulatingmember 99A, a heat conducting member 99B, a Peltier element 99C and aradiation fin 99D.

A thermocouple 97A is provided in the heat conducting member 992. Thethermocouple 97A provides an output of voltage corresponding totemperature T of the absorbent sample tube 22 to the temperature controlmeans 97. The temperature control means 97 controls feeding of power tothe Peltier element 99C so that temperature T of the absorbent sampletube 22 as given by an output from the thermocouple 97A is constant at acertain value TC. When the certain value TC is over room temperature, asimple electric heater or the like may be provided in place of thePeltier element 99C. The water absorbing filter 94 is filled with ahygroscopic agent 93 such as silica gel or calcium carbide.

When the pump 84 is operated, the breath A is sucked from the Teddlerbag 82 through the absorbent sample tube 22. As a result, the breathconstituents A are concentrated and caught by the absorbent 141 of theabsorbent sample tube 22. At this point, pressure p upon sucking ismeasured by the manometer 88, and mass flow rate is measured by the massflowmeter 86. When the Teddler bag 82 becomes empty, pressure p reachesthe level of a certain value pF, and the main control means 90 causesstoppage of the pump 84. The mass flow rate f upon completion of suckingis provided from the mass flowmeter 86 to the sucking control means 90.The sucking control means 90 therefore calculates the quantity of breathA concentrated in the absorbent sample tube 22.

Referring to FIG. 6, in the breath analyzing apparatus 12 of theinvention, the desorbing means 20, the precolumn 16 and the main column14 are connected for analysis of the concentrated breath sample. Thesample receiving tube and the sample loop 18 are connected as well tosample the breath exhaled by the subject. Further, the sample loop 18and the main column 14 are connected to analyze the breath sample suckedinto the sample loop 18. Then, the standard gas bottle 62, the sampleloop 18 and the main column 14 are connected to test sensitivity of thedetector 56 and calculate a resolution representing the columnperformance by the use of the standard gas.

Constituents of the standard gas, the breath breathed out by the subjector the breath concentrated in the absorbent sample tube are detected inthe same main column 14 and detector 56, and analyzed in the dataprocessing means 72. Adoption of the configuration shown in FIG. 6 makesit possible to analyze low-concentration and high-concentration breathconstituents, and makes it easier to carry out a test by the use of thestandard gas.

The precolumn 16, being provided for backflash, is not used for samplingbreath from the sample receiving tube. When conducting backflash, thecarrier gas should be sent to the main column while purging constituentsremaining in the precolumn. When sampling breath with the samplereceiving tube, the breath should be sucked into the sample loop bymeans of the pump at an end, and then sent to the main column by meansof the carrier gas. The configuration shown in FIGS. 1 and 2 is anembodiment permitting achievement of the steps mentioned above, but anyother configuration may be adopted, such as one based on opening/closingof the solenoid valve.

Referring to FIG. 7, the controller 44 comprises a main controller 100,temperature controller 102 for controlling the individual heaters, andline controller (channel controller) 104 for controlling switching ofthe channels. Further, in this embodiment, the apparatus comprises startcontroller 106 for controlling the breath analyzing apparatus fromstationary to a state capable of accomplishing analysis, analysiscontroller 108 for controlling analyzing operations, shutdown controller110 for discontinuing operation of the breath analyzing apparatus uponcompletion of analysis, and test controller for testing performance ofthe breath analyzing apparatus by the use of the standard gas.

Further, an interface 120 is connected to the controller 44. Theinterface 120 comprises a start button 122 for user's instructing startof the breath analyzing apparatus, an analysis start button 124 forinstructing start of analysis, an end button for instructing end ofanalysis, and a test button 128 for instructing testing. A button forswitching over between concentrated and non-concentrated types, orsetting an object to be analyzed may be provided.

Referring to FIG. 8, the temperature control means 102 is provided withpreselected temp. recorder 130 for storing set temperature and a heaterdriver 132. The recorder 130 stores temperatures forming conditions foranalysis such as a column temperature set in response to the material tobe breath-analyzed. The heater driver 132 is connected to the columnheater 14H, the detector heater 56H, the absorbent sample tube heater22H, the secondary concentrating tube heater 26H and the thermostaticoven 42H.

Referring to FIG. 9, the line controller 104 is connected to the samplevalve 42, the first carrier gas solenoid valve 50, the second carriergas solenoid valve 46, the standard gas valve 51 and the standard gasswitching valve (select valve) 43.

The controller 44 controls start, shutdown, testing and analysis of thebreath analyzing apparatus by performing control with reference to thetemperature and the switching time.

Operation

Start processing using time:

Referring to FIG. 10, when the subject presses the start button 122,start operation by the controller 44 is started. First, the controller44 selects a channel for startup, and opens the carrier gas solenoidvalves 50 and 46 (S1). The channel for starting purges the main column14 and the detector 56, and serves also as a channel for purging thedesorbing means (FIG. 2). Referring again to FIG. 2, the carrier gas,which is introduced from the desorbing means into the precolumn, may bepurged in the reverse direction from the port 8, i.e., from theprecolumn 16 to the desorbing means 20.

The timing when the solenoid valve 50 is opened is regarded as thestarting point, i.e., 0 minute. Thereafter, it is determined whether ornot a certain period of time a has elapsed (S2). As a result, thecarrier gas C purges the main column 14 and the detector 56, and then,the precolumn 16 and the desorbing means 20. This certain period of timea is for example three minutes.

After the lapse of the certain period of time a, the detector heater 56His turned on (S3; lapse of three minutes). Then, it is determinedwhether another certain period of time b has elapsed (S4). After thelapse of the certain period of time b, the column heater 14H is turnedon (S5; lapse of ten minutes). The certain period of time b is set bycomparing heating properties of the detector heater 56H and the columnheater 14H so that the detector temperature is always higher than thecolumn temperature. The certain period of time b is for example sevenminutes.

Further, it is determined whether or not a certain period of time c haselapsed (S6). After the lapse of the certain period of time c, theionization lamp 58 of the detector is turned on (S7; lapse of 13minutes). The certain period of time c should be set at a value notreducing the period of time available for the ionization lamp 58 bystabilization of operations of the ionization lamp 58 before operationsof the detector 56 are not as yet stabilized. The certain period of timec is for example three minutes.

Further, when an output signal from the detector 56 shows a value undera prescribed value (3 V for example), confirmation of slope sensitivityis started, and it is determined whether or not the slope sensitivitytakes a value under a certain value (200 μV/min for example) (S8). Whenthe slope sensitivity becomes under a certain value, a preparationcompletion signal is issued (S9; lapse of 43 minutes). As a result,preparation completion is displayed on the display 34. A slopesensitivity under the certain value means that residual constituentsleaving the main column decrease and operation of the detector 56 hasbecome stable.

Shutdown processing using time:

Referring to FIG. 11, when the operator presses the shutdown button 126,the end operation by the controller 44 is started. The controller 44selects a channel for starting and finishing from among the variouschannels for analysis. It further turns off the ionization lamp 58, andturns off the column heater 14H (S10). The moment when the column heater14H is turned off is regarded as 0 minute. Then, it is determinedwhether or not a certain period of time d has elapsed (S111). Upon thelapse of the certain period of time d, the detector heater 16H is turnedoff (S12; lapse of one minute). The certain period of time d is set bycomparing cooling properties between the detector heater 16H and thecolumn heater 14H so that the detector temperature is always higher thanthe column temperature. The period of time d is for example one minute.

Then, it is determined whether or not a certain period of time e haselapsed (S13). Upon the lapse of the certain period of time e, thesolenoid valve 18 is closed (S14; lapse of 36 minutes). The certainperiod of time e is set by taking account of the cooling property of thedetector heater 16H so as to cause degradation of performance of thedetector 56 as a result of the high-temperature detector 56 coming intocontact with the open air. The certain period of time e is for example35 minutes.

More specifically, the controller 44 controls the solenoid valve, thedetector heater, the column heater and the ionization lamp in accordancewith the time chart shown in FIG. 12, thereby achieving the foregoingflowchart.

Another example of start or end control using time:

Referring to FIG. 13, upon starting, the controller 44 turns on theionization lamp simultaneously with turn-on of the detector heater(S23). In the example shown in FIG. 13, the startup time can be reduced.Referring to FIG. 14, the controller 44 turns off the ionization lampsimultaneously with turn-off of the detector heater (S33). Thisflowchart is achieved by the controller 44 operating in accordance withthe time chart shown in FIG. 15.

Start processing using temperature:

Referring to FIG. 16, when the operator presses the start button 122,the start operation by the controller 44 is started. First, thecontroller 44 selects the channel for starting and opens the solenoidvalve (S41). The moment when the solenoid valve opens is regarded as 0minute. Then, it is determined whether or not a certain period of timehas elapsed (S42). The certain period of time is for example threeminutes. Upon the lapse of the certain period of time, the detectorheater 16H is turned on (S43; lapse of three minutes), and it isdetermined whether or not the detector 56 temperature has reached acertain percentage of the set detector temperature (S44). The setdetector temperature is stored in the set temperature storing means 130.When the temperature has reached a certain percentage, the column heater14H is turned on (S45; lapse of eight minutes). The set detectortemperature is 120° C., and the certain percentage is 60% correspondingto about 70° C. This certain percentage is set at a value such that thetemperature of the column 14 becoming higher than that of the detector56 does not impair accuracy of the detector 56.

Then, it is determined whether or not temperature of the column 14 hasreached the certain percentage of the set temperature (S46), and uponreaching the certain percentage, the ionization lamp 58 is turned on(S47; lapse of ten minutes). The set column temperature is 100° C., andthe certain percentage is 80% corresponding to 80° C. This certainpercentage is set at such a value that the available period of time forthe ionization lamp 58 is never reduced by the stabilization ofoperation of the ionization lamp 58 before stabilization of operation ofthe detector 56.

Then, when the output signal of the detector 56 shows a value under acertain value (3 V for example), confirmation of slope sensitivity isstarted, and it is determined whether or not the slope sensitivity hasbecome under a certain value (S48). When the slope sensitivity becomesunder the certain value, a preparation completion signal is generatedfor output (S49; lapse of 37 minutes). As a result, preparationcompletion is displayed on the display.

Shutdown processing using temperature:

Referring to FIG. 17, when the operator presses the shutdown button 126,end operation by the controller 44 is started. First, the controller 44selects a channel for start and end, turns off the ionization lamp 58,and turns off the column heater 14H (S51). This is regarded as thestarting point, i.e., 0 minute. Then, it is determined whether or nottemperature of the column 12 has reached a certain percentage of the setcolumn temperature (S52), and when it decreases to the certainpercentage, the detector heater 56H is turned off (S53; lapse of oneminute). The set column temperature is 100° C., and the certainpercentage is 70% corresponding to 70° C. This certain percentage is setat such a value that accuracy of the detector 56 is never degraded bythe temperature of the detector 56 becoming lower than that of thecolumn 12.

Then, it is determined whether or not temperature of the detector 56 hasdecreased to the certain percentage of the set detector temperature(S54). When it decreases to the certain percentage, it is determinedwhether or not a certain period of time has elapsed (step S55; lapse of31 minutes). Upon the lapse of the certain period of time, the solenoidvalve is closed (S56; lapse of 36 minutes). The set detector temperatureis 120° C., and the certain percentage is about 17% corresponding to 20°C. The certain period of time is five minutes. The certain percentageand the certain period of time are set at such values that performanceof the detector 56 is never degraded by the high-temperature detector 56exposed to the open air. Start and end control using temperature resultsin a time chart for example as shown in FIG. 18.

Concentrated type test processing:

Referring to FIG. 19, when the test button 128 is pressed, thecontroller 44 tests the column 14 and the detector 56. First, the valve42 is driven to the second operating position as shown in FIG. 2, andthe solenoid valve is opened. Then, the carrier gas C is sent throughthe sample loop 18 to the main column 14 and the detector 56. Then,slope sensitivity of the detector 56 is measured (S61). Typical testconditions include a column 12 temperature of 80° C., a detector 56temperature of 120° C. and a carrier gas C comprising helium at 6ml/min.

Then, the sample valve 42 is switched over to the first operatingposition as shown in FIG. 1. The standard gas valve 43 is switched overand the solenoid valve 48 is opened to standard gas in a certainquantity is introduced into the sample loop 18. Further, the samplevalve 42 is switched over to the second operating position as shown inFIG. 2. Then, the solenoid valve 46 is opened to send the standard gas Sintroduced into the sample loop to the main column 14 and the detector56.

Since the standard gas contains pentane and isoprene in concentrationscontained in the breath sample desorbed in the desorbing means 22, themain column 14 separates these constituents in response to therespective retention times. The detector 56 generates electric signalsdependent on the content of each constituent by ionizing the breathconstituents by irradiating, for example, the ionization lamp 58.Further, the data processor 72 calculates resolutions fromchromatographs of pentane and isoprene (S62).

Referring to FIG. 20, the extent of separation of the two constituentscannot be known from the separation coefficient k (the keeping ratio ofthe latter constituent relative to the former constituent, k>1) and thesteepness of peaks of both constituents (theoretical number of steps, N)alone. An extent of separation can be expressed by a resolution R. InFIG. 20, R is given by:

R=2(tr 2−tr 1)/(w 1−w 2)

The following formula can be derived as a formula correlating R with N,k and k′ on the assumption of w1=w2:

R=(N 1/2/4)[k−1)/α[k′/(k′+1)]

When R<0.5, two peaks almost overlap each other, R=1 leads to partialoverlap of 2%, and R=1.25, to overlap of 0.5%. With R=1.5, separation issubstantially complete.

Then, it is determined whether or not sensitivity of the detector 56 andresolution of the column 12 are normal (S63). A sensitivity of thedetector 56 as represented by a slope sensitivity under a certain value(200 μV for example) is normal, and one over the certain value isabnormal. A column 12 resolution of over a certain value is normal, andone under the certain value is abnormal. The certain value forresolution is equal to a threshold value of 1.5 when the standard gascomprises a combination of helium with isoprene and pentane.

If sensitivity of the detector 56 or resolution of the column 14 isabnormal, the column 14 and the detector 56 are conditioned (S64).Conditioning is carried out by supplying the carrier gas for a certainperiod of time while heating the main column 14 and the detector 56.Referring to FIG. 21, the carrier gas is supplied for 960 minutes. Inthis supply, temperature of the column 14 is varied within a range offrom 50° C. to near the maximum temperature. Temperature of the detector56 is kept constant. Of the carrier gas C, helium is supplied at 6ml/min.

Upon completion of this conditioning, sensitivity of the detector 56 istested again (S65), and resolution of the column 12 is tested (S66), todetermine whether or not sensitivity of the detector 56 and resolutionof the column 12 are normal (S67). When sensitivity of the detector 56or resolution of the column 12 is abnormal, this is displayed on thedisplay 34 (S68). The display tells, when sensitivity of the detector 56is abnormal, that “The detector may deteriorate. Check or replace thedetector.” and when resolution of the column 12 is abnormal, that “Thecolumn may deteriorate. Check or replace the column.” As required,execution of automatic end causes end of all the operations (S69).

When no abnormality is found in steps S64 and S67, execution ofautomatic end (S69) causes end of all the operations.

In an embodiment, timing of starting test is not only pressing the testbutton 128, but the column 14 and the detector 56 are tested at everylapse of a prescribed period of time or every end of a prescribed numberof analyzing runs. The prescribed period of time in this case is forexample one day, and the prescribed number runs of analysis is forexample one span. One span means a number of runs of analysis whencontinuously analyzing the same constituent, or when continuouslyanalyzing under the same conditions. A test may be carried out uponevery end processing.

Concentrated type analyzing processing:

Prior to starting analysis, the operator should previously cause theabsorbent sample tube 22 to absorb the breath sample A by means of thebreath concentrating/absorbing apparatus 80 shown in FIG. 5. Then, theabsorbent sample tube 22 is attached to the desorbing means 20. When theoperator presses the analysis start button, the controller 44 startsbreath analysis. When startup has not as yet been conducted, the startprocessing is performed first. Upon completion of startup, the carriergas flows constantly to purge the column 14 and the detector 56. Thedetector 56 always provides an output of detection signal ofconstituents to the data processor 72. Referring to FIG. 22, uponstarting analysis, a start signal is sent to the data processor 72(S71). Then, the data processor 72 stores the output signal from thedetector 56.

Then, the controller switches over the channel from the purging channelto that shown in FIG. 1 (S72). Then, the breath sample absorbed in theabsorbent sample tube is desorbed. Appearance of a peak in thechromatograph varies with the manner of desorbing. That is, a gradualdesorbing result in an excessively wide band, preventing satisfactoryquantitative determination. In this embodiment, therefore, a secondaryconcentration is performed.

Referring to FIG. 23, the desorbing processing S73 comprises heating theabsorbent sample tube 22 for example to 250° C. (S81), and at the sametime, cooling the secondary concentrating tube 26 for example to atemperature within a range of from −130 to −180° C. (S82). When thecarrier gas C is passed from the absorbent sample tube 22 to thesecondary concentrating tube 26, the breath sample A leaves theabsorbent sample tube 22, is further concentrated, and absorbed by thesecondary concentrating tube 26. Upon completion of absorption of thebreath sample A into the secondary concentrating tube 26, i.e., upon thelapse of a certain period of time j (S83), the secondary concentratingtube 26 is heated for example to 190° C. (S84).

Referring again to FIG. 1, at this point, the solenoid valve 46 isclosed to saving the carrier gas C. The carrier gas C1 therefore flowsthrough the solenoid valve 50, the desorbing means 20, the filter 30,the ports 10 and 9, the precolumn 16, the parts 1 and 2, the main column14, and the detector 56, and then discharged. The breath sample A flowas well with the carrier gas C, and passes through the precolumn 16, themain column 14 and the detector 56. Constituents contained in the breathsample A are separated in the precolumn 16 and the main column 14, andare thus detected by the detector 56 with time changes.

In the concentrated type, it is possible to detect low-concentrationhigh-boiling-point constituents (such as hexane) which cannot bedetected in the non-concentrated type. However, ordinaryhigh-boiling-point constituents have a long retention time in theprecolumn 16 and the main column 14 (delay in retention). As a result,the time required for analysis, which is for example 15 minutes in thenon-concentrated type, is more than an hour in the concentrated type.

Referring to FIG. 24, pentane P is detected in about six minutes fromthe start of analysis, and hexane H is detected in about 30 minutes.Even when only pentane P must be detected, therefore, it is necessary tocontinue analysis for a long period of time for discharging hexane. Topass a high-boiling-point constituent such as hexane through the maincolumn 14 and the detector 56 may lead to contamination or deteriorationof these components.

For the purpose of reducing the analyzing time and preventingcontamination and deterioration, therefore, backflash is conducted. Asshown in FIG. 25(A), when the carrier gas C1 begins flowing through theprecolumn 16 and the main column 14, pentane P and hexane H, which areconstituents of the breath sample A, enters the precolumn 16. Pentane Pwhich is harder to be held in the precolumn 16 than hexane H passesthrough the precolumn 16 before hexane as shown in FIG. 25(B). As timepasses and even when pentane P has advanced considerably into the maincolumn 14, hexane still remains in the precolumn 16, as shown in FIG.25(C). If the carrier gas C1 continues to flow in this state, it takes along time for hexane H to leave the main column 14. Therefore, theprecolumn 16 and the main column 14 are separated, and a carrier gas C3in the reverse direction to the carrier gas C1 is caused to flow in theprecolumn 16. The carrier gas C2 is caused to flow in the same directionas that of the carrier gas C1 in the main column 14. As a result,pentane P is detected upon leaving the main column 14, and hexane H ispurged from the precolumn 16, as shown in FIG. 25(D).

When the column length, temperature thereof and the carrier gas flowrate are constant, the retention time of the breath constituents in thecolumn is also constant. Purging of the precolumn shown in FIG. 25(D) isaccomplished upon the lapse of a certain period of time g from the startof desorption.

Referring again to FIG. 22, upon the lapse of this certain period oftime g (S74), pentane P stays in the main column 14, and hexane H, inthe precolumn 16. The valve 42 is changed from FIG. 1 to FIG. 2 (S75).Upon further lapse of a certain period of time h, for example in thecase shown in FIG. 24, the channel is switched over to that for purgingthe main column 14 and the detector 56 when three minutes have elapsedfrom the change into the backflush channel and eight minutes from thestart of analysis (S77). In the example shown in FIG. 2, purging isaccomplished by causing the carrier gas to flow without changing thechannel.

In the detector 56, a qualitative analysis is carried out on the basisof the capacity (holding capacity) of carrier gas or the time (retentiontime) thereof before formation of discriminating bands of the individualconstituents after pouring of the breath sample A, and a quantitativeanalysis, on the basis of the peak area or the peak height.

Non-concentrated type test processing:

First, the sample receiving tube 32 is heated for example to 40° C., andthe channel shown in FIG. 1 is selected. When the subject presses theanalysis start button and blows breath B into the sample receiving tube32, the pump 66 operates only for a prescribed period of time inresponse thereto. In this case, the breath B flows through the samplereceiving tube 32, the ports 5 and 6, the sample loop 18, the ports 3and 4, and the pump 66, and is then discharged. As a result, the sampleloop 18 is filled with the breath B as the breath sample A.

When the breath is sucked into the sample loop 18, the channel shown inFIG. 2 is selected to cause the carrier gas to flow therethrough. As thesolenoid valve 46 is open at this point, the carrier gas C2 flowsthrough the solenoid valve 46, the ports 7 and 6, the sample loop 18,the ports 3 and 2, and the main column 14 and the detector 56, and isthen discharged. The breath sample A filling the sample loop 18 flowstogether with the carrier gas C2, and passes through the main column 14and the detector 56. The constituents contained in the breath sample Aare detected by the detector 56 with time changes as a result ofseparation in the main column 14.

Analytical conditions:

Concentration of dimethyl sulfide in the breath is believed to increaseas a result of hepatocirrhosis or the like. Isoprene is a precursor ofcholesterol, and the concentration thereof in breath is said to increaseas a result of diabetes mellitus, hypertension diseases, cholelithiasisor arteriosclerosis. In pregnant intoxication, diabetes mellitus andarteriosclerosis, lipid peroxidation causes an increase in the pentaneconcentration in breath. By conducting concentration, using a PLOT(porous layer open tubular) column having a high liquidus polarity (forexample, poraplot U), and setting the following conditions including acolumn temperature, a column length and a carrier gas flow rate, it ispossible to satisfactorily separate pentane, isoprene and dimethylsulfide in the foregoing breath analyzing apparatus.

The conditions for the main column 14 include, for example, a materialcomprising molten silica, an inside diameter within a range of from 0.3to 1.0 [mm], a length of from about 10 to 25 [m], a coating layerthickness of from 10 to 20 [μm], a coating layer material comprisingdivinylbenzene ethylene glycol dimethacrylate. A layer length of themain column generally leads to a better resolution, but on the contrary,to a longer period of time required for analysis. A length within arange of from 10 to 25 [m] is therefore appropriate. As the detector 56,a flame ionization detector (FID) or a thermal conductivity detector(TCD) may be used.

The breath analyzing apparatus shown in FIGS. 1 and 2 is employed. Sincedetection of pentane, dimethyl sulfide and isoprene should preferably beconducted after concentration, the sample receiving tube 32 or thesample loop 18 is not necessary for analyzing these three substancesalone. A breath analyzing apparatus not having a sample receiving tube32 is illustrated in FIGS. 26 and 27. In this example, a sampling valve42 having eight ports is used. The carrier gases C1 to C3 upon backflashare shown in FIGS. 26 and 27. Referring to FIG. 28, the sectional viewof the sampling valve 42 is substantially the same as that shown in FIG.4.

Referring to FIG. 29, E represents a peak of ethanol, D, dimethylsulfide, P, pentane, and I, isoprene (the same applies hereafter also inthe following chromatograms). In FIG. 29, for pentane and dimethylsulfide, the retention times become reverse under some conditions. FIG.29[a] illustrates a case where the retention time for pentane is longerthan that for dimethyl sulfide, and FIG. 29[b] covers a case where theretention time for pentane is shorter than that for dimethyl sulfide.

As is clear from FIG. 29, R12 indicates resolution for ethanol anddimethyl sulfide or pentane, R23, resolution for dimethyl sulfide andpentane, and R34, resolution for dimethyl sulfide or pentane andisoprene. As described above, reversal of the retention time betweendimethyl sulfide and pentane does not affect calculation of resolutionR23.

Pentane, main column length of 10 m:

Referring to FIG. 30, a higher column temperature results in a shorterretention time for all the three constituents. Referring to FIG. 31,with a column temperature of 110° C., a higher flow rate leads to ashorter retention time for all the three constituents. Referring to FIG.32, with a column temperature of 130° C., a higher flow rate bringsabout a sudden decrease in the retention time for all the threeconstituents. Referring to FIG. 33, resolution of each constituentvaries with the column temperature.

Referring to FIG. 33, according to the analysis of pentane, the maincolumn temperature should preferably be within a range of from 125 to135° C., or more preferably, 130° C. Within this temperature range, theretention time of dimethyl sulfide is longer than that of pentane (FIG.36), this corresponding to the chromatogram shown in FIG. 29[b].Therefore, R12 is the resolution for ethanol and pentane, and R23 is theresolution for pentane and dimethyl sulfide. The lower limit value isset at 125° C. because a temperature under 125° C. leads to an R23 ofunder 1.3, although R12 is over 1.5 as shown in FIG. 33. The upper limitvalue is set at 135° C. because a temperature over 135° C. results in anR12 value under 1.3 although R23 is over 1.5, as shown in FIG. 33.

Referring to FIG. 35, the carrier gas flow rate should preferably bewithin a range of from 3 to 6 [ml/min.], or more preferably, 5[ml/min.]. At a temperature of 130° C., the retention time of dimethylsulfide is longer than that of pentane as shown in FIG. 36, taking theform of the chromatogram shown in FIG. 29[b]. Therefore, R12 is theresolution for ethanol and pentane, and R23 is the resolution forpentane and dimethyl sulfide. The lower limit is set at 3 [ml/min.]because a value under 3 [ml/min.] leads to an R12 of under 1.5 and anR23 of under 1.4 as shown in FIG. 35. The upper limit value is set at 6[ml/min.] because a value of over 6 [ml/min.] results in an R23 of under1.4 although R12 is over 1.5, as shown in FIG. 35.

FIG. 36 is a graph illustrating relative retention times for theindividual constituents relative to the main column temperature. Theterm relative retention time as used herein means the retention time foreach constituent on the assumption of a retention time of ‘1’ forethanol.

Pentane, main column length of 25 m:

Referring to FIG. 37, the retention time is reduced by increasing thecolumn temperature also in the case of a column length of 25 m.Similarly, referring to FIG. 38, an increased flow rate results in ashorter retention time. Referring to FIG. 39, a higher flow rate leadsto a shorter retention time also in the case of a column temperature of110° C.

Referring to FIG. 40, resolution varies with the column temperature onthe assumption of a column length of 25 m and a flow rate of 5[ml/min.]. When analyzing pentane with a column length of 25 m, the maincolumn temperature should preferably be within a range of from 85 to115° C., or more preferably, from 90 to 110° C. Within this temperaturerange, the retention time of pentane is longer than that of dimethylsulfide as shown in FIG. 43, resulting in a chromatogram as shown inFIG. 29[a]. Therefore, R23 is the resolution for dimethyl sulfide andpentane, and R34 is the resolution for pentane and isoprene. The lowerlimit value is set at 85° C. because a value under 85° C. is found totend to result in an R34 of under 1.5 although R23 is oven 2.0 as shownin FIG. 40. The upper limit value is set at 115° C. because atemperature of over 115° C. leads to an R23 of under 1.6 although R34 isover 2.4.

The carrier gas flow rate should preferably be different between a maincolumn temperature range of from 85 to 105° C. and a main columntemperature range of from 105 to 115° C. Within the main columntemperature range of from 85 to 105° C., as shown in FIG. 40, thecarrier gas flow rate should preferably be within a range of from 2 to25 [ml/min.], or more preferably, from 5 to 20 [ml/min.].

The upper limit value is set at 25 [ml/min.] because a flow rate of over25 [ml/min.] causes a decrease in R23 and R34, as shown in FIG. 41.Within the main column temperature range of from 105 to 115° C., thecarrier gas flow rate should preferably be within a range of from 2 to10 [ml/min.], or more preferably, 5 [ml/min.], as shown in FIG. 42. Theupper limit value is set at 10 [ml/min.] because a flow rate of over 10[ml/min.] leads to an R23 of under 1.4 although R34 is over 2.0 as shownin FIG. 42.

Dimethyl sulfide, main column length of 10 m:

Referring again to FIG. 33, when analyzing dimethyl sulfide with a maincolumn length of 10 m, the main column temperature should preferably bewithin a range of from 125 to 140° C., or more preferably, 130° C.Within this temperature range, the retention time of dimethyl sulfide islonger than that of pentane as shown in FIG. 36, resulting in achromatogram as shown in FIG. 29[b]. Therefore, R23 is the resolutionfor pentane and dimethyl sulfide, and R34 is the resolution for dimethylsulfide and isoprene. In order to ensure clear separation of dimethylsulfide, both R23 and R34 must be at least certain values. The lowerlimit value is set at 125° C. because a value of under 125° C. resultsin an R23 of under 1.3 as shown in FIG. 33. The upper limit value is setat 140° C. because a value of over 140° C. leads to an R34 of under 1.3as shown in FIG. 33.

In this case, the carrier gas flow rate should preferably be within arange of from 3 to 6 [ml/min.], or more preferably, 5 [ml/min.]. Thelower limit value is set at 3 [ml/min.] because a value of under 3[ml/min.] results in an R23 of under 1.4 as shown in FIG. 35. The upperlimit value is set at 6 [ml/min.] because a value of over 6 [ml/min.]leads to an R23 of under 1.4 as shown in FIG. 35.

Dimethyl sulfide, main column length of 25 m:

Referring again to FIG. 40, when analyzing dimethyl sulfide with acolumn length of 25 m, the main column temperature should preferably bewithin a range of from 80 to 115° C., or more preferably, from 90 to110° C. Within this temperature range, the retention time of pentane islonger than that of dimethyl sulfide as shown in FIG. 43, resulting in achromatogram as shown in FIG. 29[a]. Therefore, R12 is the resolutionfor ethanol and dimethyl sulfide, and R23 is the resolution for dimethylsulfide and pentane. In order to ensure clear separation of dimethylsulfide, both R12 and R23 must be at least certain values. The lowerlimit value is set at 80° C. because a temperature of under 80° C. tendsto give an R12 of under 1.5 as shown in FIG. 40. The upper limit valueis set at 115° C. because a temperature of over 115° C. results in anR23 of under 1.6.

When analyzing dimethyl sulfide with a column length of 25 m, thecarrier gas rate should preferably vary between the main columntemperature range of from 80 to 105° C. and the range thereof of from105 to 115° C. At a main column temperature within the range of from 80to 105° C., the carrier gas flow rate should preferably be within arange of from 2 to 25 [ml/min.], or more preferably, from 5 to 20[ml/min.] as shown in FIG. 41. At a temperature of 100° C. as shown inFIG. 23, the retention time of pentane is longer than that of dimethylsulfide as shown in FIG. 43, resulting in a chromatogram as shown inFIG. 29[a]. Therefore, R12 is the resolution for ethanol and dimethylsulfide, and R23 is the resolution for dimethyl sulfide and pentane. Toensure clear separation of dimethyl sulfide, both R12 and R23 must be atleast a certain value. The lower limit value is set a 2 [ml/min.]because a flow rate of under 2 [ml/min.] cannot give a sufficient signalintensity. The upper limit value is set at 25 [ml/min.] because a flowrate of over 25 [ml/min.] tends to give an R23 of under 1.5 as shown inFIG. 41. At a main column temperature within the range of from 105 to115° C., the carrier gas flow rate should preferably be within a rangeof from 2 to 10 [ml/min.], or more preferably, 5 [ml/min.] as shown inFIG. 42. The upper limit value is set at 10 [ml/min.] because a flowrate of over [ml/min.] results in an R23 of under 1.4.

Isoprene, main column length of 10 m:

Referring again to FIG. 33, when analyzing isoprene with a column lengthof 10 m, the main column temperature should preferably be within a rangeof from 20 to 140° C., or more preferably, from 30 to 130° C. Withinthis temperature range, as shown in FIG. 36, the retention time ofisoprene is always longer than that of dimethyl sulfide or pentane,resulting in a chromatogram shown in FIG. 29[a] or 29 [b]. Therefore,R34 is the resolution for isoprene and dimethyl sulfide or pentane. Toensure clear separation of isoprene, R34 must be at least a certainvalue. The lower limit value is set at 20° C. (room temperature) becausea lower temperature only leads to a longer retention time as shown inFIG. 30, and is not considered to affect separation of isoprene from theother constituents as shown in FIG. 30. The upper limit value is set at140° C. because a temperature of over 140° C. leads to an R34 of under1.3 as shown in FIG. 33.

As shown in FIG. 35, the carrier gas flow rate should preferably bewithin a range of from 2 to 10 [ml/min.], or more preferably, 6[ml/min.]. At a temperature of 130° C. as shown in FIG. 35, theretention time of dimethyl sulfide is longer than that of pentane asshown in FIG. 36, resulting in a chromatogram shown in FIG. 29[b].Therefore, R34 is the resolution for dimethyl sulfide and isoprene. Toensure clear separation of isoprene, R34 must be at least a certainvalue. The lower limit value is set at 2 [ml/min.] because a flow rateof under 2 [ml/min.] leads to an R34 of under 1.6 as shown in FIG. 35.The upper limit value is set at 10 [ml/min.] because a flow rate of over10 [ml/min.] leads to an R34 of under 1.6 as shown in FIG. 35.

Isoprene, column length of 25 m:

Referring again to FIG. 40, when analyzing isoprene in a main columnhaving a length of 25 m, the main column temperature should preferablybe within a range of from 80 to 150° C., or more preferably, from 90 to110° C. Within this temperature range, as shown in FIG. 43, theretention time of isoprene is always longer than that of dimethylsulfide or pentane, resulting in a chromatogram shown in FIG. 29[a] or29[b]. Therefore, R34 is the resolution for isoprene and dimethylsulfide or pentane. To ensure clear separation of isoprene, R34 must beat least a certain value. The lower limit value is set at 80° C. becausea temperature of under 80° C. tend to give an R34 of under 1.5 as shownin FIG. 40. The upper limit value is set at 150° C. because a value ofover 150° C. gives an R34 of under 1.6 as shown in FIG. 40.

As shown in FIG. 41, the carrier gas flow rate should preferably bewithin a range of from 2 to 25 [ml/min.], or more preferably, from 5 to20 [ml/min.]. At a temperature of 100° C. as shown in FIG. 22, theretention time of pentane is longer than that of dimethyl sulfide asshown in FIG. 43, resulting in a chromatogram as shown in FIG. 29[a].Therefore, R34 is the resolution for pentane and isoprene. To ensureclear separation of isoprene, R34 must be at least a certain value. Thelower limit value is set at 2 [ml/min.] because a flow rate of under 2[ml/min.] leads to unavailability of a sufficient signal intensity. Theupper limit value is set at 25 [ml/min.] because a value of over 25[ml/min.] tends to give an R34 of under 1.6 as shown in FIG. 22.

Referring to FIGS. 44 to 47, it is possible to obtain a satisfactorychromatogram at a temperature set in response to the particular use.

The results of optimization of analytical conditions have been describedabove for cases where main columns 14 having lengths of 10 [m] and 25[m] are used. When considering the difference in performance of the maincolumn 14 based on the difference in length of the main column 14,results similar to those obtained with the main column 14 having alength of 10 [m] are considered to be available under the foregoinganalytical conditions even when using a main column having a lengthwithin a range of from 8 to 12 [m], and even for a main-column having alength within a range of from 20 to 30 [m], similar results as those ofthe main column 14 having a length of 25 [m] are considered to beavailable under the foregoing analytical conditions.

The above-mentioned temperature and flow rate are controlled by means ofthe controller 44.

The entire disclosure of Japanese patent Applications:

No. 7-270533 filed on Sep. 25, 1995;

No. 7-319553 filed on Nov. 14, 1995;

No. 8-073208 filed on Mar. 4, 1996;

No. 8-191342 filed on Jul. 2, 1996;

No. 8-231371 filed on Aug. 13, 1996;

No. 8-231372 filed on Aug. 13, 1996; and

No. 9-145846 filed on May 20, 1997,

including the specification, claims, drawings and summary areincorporated herein by reference in its entirety.

What is claimed is:
 1. An apparatus for analyzing a breath sample, theapparatus comprising: (a) desorbing apparatus for desorbing a breathsample absorbed into an absorbent sample tube; (b) a chromatographicprecolumn for passing the breath sample desorbed from the absorbentsample tube in a retention time prescribed for each constituent; (c) asample receiving tube for receiving the exhaled breath sample; (d) asample loop for aspirating a prescribed quantity of breath sample fromthe sample receiving tube; (e) a chromatographic main column for passingthe breath sample having passed through the precolumn or the sampleloop, in a retention time prescribed for each constituent; (f) adetector for detecting constituents having passed through the maincolumn; (g) a data processor for generating a chromatograph for theconstituents detected by the detector; (h) a sample valve which connectsthe sample loop and the main column when a breath sample is aspiratedinto the sample loop; (i) a standard gas bottle for supplying a standardgas; (j) a standard gas valve which connects the standard gas bottle andthe sample loop when testing sensitivity of the main column. 2.Apparatus according to claim 1, further comprising: (a) a carrier gasbottle; (b) a first carrier gas line for carrying the breath sampleaspirated into the sample loop to the sample valve, the main column andthe detector; (c) a second carrier gas line for carrying the breathsample desorbed from the absorbent sample tube to the sample valve, theprecolumn, the main column and the detector; (d) a first solenoid valveprovided between the first carrier gas line and the carrier gas bottle;and (e) a second solenoid valve provided between the second carrier gasline and the carrier gas bottle.
 3. Apparatus according to claim 2,further comprising: (a) a third carrier gas line for carrying thestandard gas aspirated into the sample loop to the sample valve, themain column and the detector; and (b) a third solenoid valve providedbetween the third carrier gas line and the standard gas bottle. 4.Apparatus according to claim 3, further comprising: (a) a fourth carriergas line which carries the constituents having passed through theprecolumn in the breath sample desorbed from the absorbent sample tube;(b) a fifth carrier gas line which purges the constituents not havingpassed through the precolumn in the breath sample desorbed from theabsorbent sample tube; and (c) wherein said sample valve comprises: (i)a first operating position for selecting said second carrier gas line;and (ii) a second operating position for selecting said fourth and thefifth carrier gas lines.
 5. Apparatus according to claim 4, furthercomprising: (a) a detector heater for heating the detector; and (b) acolumn heater for heating the precolumn and the main column. 6.Apparatus according to claim 5, further comprising: (a) a controllerhaving a temperature control unit for heating the detector heater andthe column heater to a predetermined temperature prior to startinganalysis.
 7. The apparatus of claim 6, wherein the standard gascomprises hexane and pentane.
 8. Apparatus according to claim 6, furthercomprising: (a) input apparatus comprising: (i) a start button forinstructing start; (ii) an analysis start button for instructing startof analysis; (iii) a shutdown button for instructing shutdown; and (iv)a test button for instructing a test; and (b) wherein said controllercomprises: (i) a start controller which purges said columns whenreceiving a start signal from the start button and heats said detectorheater and said column heater to a predetermined temperature; (ii) ananalysis controller which desorbs a breath sample or aspirates a breathwhen receiving an analysis start signal from the analysis start buttonand switches over said first to fifth gas lines; (iii) a shutdowncontroller which reduces temperature of said detector heater and saidcolumn heater and discontinues supply of the carrier gas when receivinga shutdown signal from the shutdown button; and (iv) a test controllerwhich tests sensitivity and resolution of the detector with the standardgas when receiving a test signal from the test button.
 9. Apparatusaccording to claim 8, further comprising: (a) a display connected to thecontroller; (b) said start controller displaying a message ofpreparation completion on the display upon completion of startcontroller; and (c) said test controller displaying a message of testresult on the display upon completion of test controller.
 10. Apparatusaccording to claim 1, wherein said desorbing apparatus comprises: (a) anabsorbent sample tube heater which heats the absorbent sample tube todesorb the breath sample absorbed in said absorbent sample tube; (b) asecondary concentrating tube for absorbing the breath sample in theinterior thereof; (c) a secondary concentrating tube cooler which coolsthe secondary concentrating tube for absorbing into said secondaryconcentrating tube the breath sample desorbed from said absorbent sampletube; and (d) a secondary concentrating tube heater which heats thesecondary concentrating tube for desorbing the breath sample absorbed insaid secondary concentrating tube.
 11. Apparatus according to claim 1,wherein: (a) said data processor comprises apparatus for subjecting thedetection result of said standard gas to a data processing to calculatesensitivity and resolution of the main column.
 12. Apparatus accordingto claim 1, further comprising: (a) a rotary valve having ten ports andlines for connecting adjacent ports; (b) a carrier gas bottle; (c) afirst carrier gas line which connects the carrier gas bottle and thedesorbing means; (d) a first valve provided in the first carrier gasline; (e) a second carrier gas line which connects the carrier gasbottle and ports of said rotary valve; (f) a second valve provided inthe second carrier gas line; (g) said ports being connected sequentiallyfrom the first port: (i) an end of the precolumn; (ii) an end of themain column; (iii) an end of the sample loop; (iv) a pump; (v) thesample receiving tube; (vi) the other end of the sample loop; (vii) thesecond carrier gas line; (viii) a vent; (ix) the other end of theprecolumn; and (x) the desorber; (h) said rotary valve having a firstoperating position and a second operating position; (i) the firstoperating position connecting: an end of the precolumn and an end of themain column; an end of the sample loop and the pump; the samplereceiving tube and the other end of the sample loop; the second carriergas line and the vent; and the other end of the precolumn and thedesorber; and (ii) the second operating position connecting: thedesorber and an end of the precolumn; an end of the main column and anend of the sample loop; the pump and the sample receiving tube; theother end of the sample loop and the second carrier gas line; and thevent and the other end of the precolumn.
 13. An apparatus for analyzinga breath sample, the apparatus comprising: (a) desorbing apparatus fordesorbing a breath sample absorbed in an absorbent sample tube: (b) achromatographic precolumn for passing the breath sample desorbed fromthe absorbent sample tube in a retention time prescribed for eachconstituent; (c) a sample receiving tube receiving the breath sample;(d) a sample loop aspirating the breath sample from the sample receivingtube; (e) a chromatographic main column for passing the breath samplehaving passed through the precolumn or the sample loop, in a retentiontime prescribed for each constituent; (f) a column heater which heatsthe main column and the precolumn to a prescribed temperature; (g) adetector detecting the constituents having passed through the maincolumn; (h) a detector heater heating the detector to a preselectedtemperature; (i) a data processor generating a chromatograph of theconstituents detected by the detector; (j) a sample valve which connectsthe sample loop and the main column when a breath sample is aspiratedinto the sample loop; and (k) a controller comprising: (i) column heatcontrol apparatus which heats said column heater to a preselectedtemperature in response to the length of the main column; (ii) detectorheat control apparatus for heating the detector to a preselectedtemperature; and (iii) completion timing apparatus for settingcompletion timing of analysis with reference to the retention time inresponse to a preselected temperature and the object of analysis.
 14. Anapparatus for analyzing a breath sample, the apparatus comprising: (a)desorbing apparatus for desorbing breath sample absorbed into anabsorbent sample tube: (b) a chromatographic precolumn for passingbreath sample desorbed from the absorbent sample tube in a retentiontime prescribed for each constituent; (c) a sample receiving tubereceiving exhaled breath sample; (d) a sample loop for aspirating aprescribed quantity of breath sample from the sample receiving tube; (e)a chromatographic main column for passing breath sample having passedthrough the precolumn or the sample loop, in a retention time prescribedfor each constituent; (f) a detector for detecting constituents havingpassed through the main column; (g) a data processor for generating achromatograph for the constituents detected by the detector; (h) asample valve comprising a first position which connects the sample loopand the main column when breath sample is aspirated into the sample loopand a second position which connects the precolumn to the main column;(i) a standard gas bottle for supplying a standard gas; (j) a standardgas valve which connects the standard gas bottle and the sample loopwhen testing sensitivity of the main column.